This project will investigate immunologic mechanisms of glomerular injury using the complement-independent nephrotoxic nephritis model in the guinea pig and Heymann nephritis model of experimental membranous nephropathy in the rat. The role of glomerular polyanion in alterations in glomerular permeability will be investigated using histochemical techniques as well as by measuring fractional clearances of differently charged protein molecules. Mechanisms regulating the subepithelial localization of immune deposits will be studied in the passive Heymann nephritis model induced by injection of heterologous antibody to rat renal tubular epithelial antigen. Deposits will be studied by immunofluorescent, ultrastructural and radiolabelling techniques during alterations of systemic factors (antigen:antibody ratio, vasoactive amine blockade, complement depletion) and local (altered glomerular permeability) factors. The role of complement and polymorphonuclear leukocytes in mediating the alteration in glomerular permeability induced by subepithelial immune deposits will be defined. The isolated perfused kidney system will be utilized to study directly the possibility that subepithelial immune deposits in membranous nephropathy represent in situ complex formation, to define the factors regulating localization of deposits at this site and to study mechanisms of proteinuria in experimental glomerulonephritis.